Circular RNAs (circRNAs) from back-spliced exon(s) are characterized by the covalently closed loop feature with neither 5' to 3' polarity nor polyadenylated tail. Recently, over ten thousand different circular RNAs have been archived across various cell lines, tissues and species.

Although unfavorably processed in general, circRNA biogenesis from back-splicing can be facilitated by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon(s). Expression levels of circRNAs from the same loci are diverse in different cell lines and tissues with the same cis-elements, suggesting the involvement of trans-factors on regulation of circRNA expression.

Some circRNAs are found to shape gene expression by titrating microRNAs, regulating transcription and interfering with splicing, but the function of the majority of circRNAs remains to be further explored.

A research group led by Dr. CHEN LingLing at Shanghai Institute of Biochemistry and Cell Biology of Chinese Academy of Sciences (CAS), collaborating with a research group led by Dr. YANG Li at CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences of CAS, reported a most recent progress on circRNA biogenesis and function. They demonstrated a coordinated regulation of circRNA biogenesis and function by NF90/NF110 in viral infection. The study was published in Molecular Cell.

Researchers applied a genome-wide siRNA screening with an efficient circRNA expression reporter to show that over 100 RBPs had the potential to interfere with circRNA expression, such as NF90/NF110. The mechanistic studies suggested that NF90 and its 110 isoform NF110 (NF110) could promote circRNA production by stabilizing intronic RNA pairs in the nucleus.

They further found that NF90/NF110 were also components of circRNPs in the cytoplasm. Upon viral infection, nascent circRNA expression was decreased, at least partially due to the export of NF90/NF110 to the cytoplasm. Meanwhile, the de-association of NF90/NF110 from circRNPs in the cytoplasm allowed their binding to viral mRNAs to inhibit viral replication.

This study revealed a role of NF90/NF110 in circRNA biogenesis and function in viral infection. It was supported by the grants from the CAS, National Natural Science Foundation of China, and Ministry of Science and Technology.